Lower female survival from an opportunistic infection reveals progesterone-driven sex bias in trained immunity.

Immune responses differ between females and males, although such sex-based variance is incompletely understood. Observing that bacteremia of the opportunistic pathogen Burkholderia gladioli caused many more deaths of female than male mice bearing genetic deficiencies in adaptive immunity, we determined that this was associated with sex bias in the innate immune memory response called trained immunity. Female attenuation of trained immunity varies with estrous cycle stage and correlates with serum progesterone, a hormone that decreases glycolytic capacity and recall cytokine secretion induced by antigen non-specific stimuli. Progesterone receptor antagonism rescues female trained immune responses and survival from controlled B. gladioli infection to magnitudes similar to those of males. These data demonstrate progesterone-dependent sex bias in trained immunity where attenuation of female responses is associated with survival outcomes from opportunistic infection.

In Vivo Imaging of Oncolytic Measles Virus Propagation with Single-Cell Resolution.

Recombinant measles viruses (MVs) have oncolytic activity against a variety of human cancers. However, their kinetics of spread within tumors has been unexplored. We established an intravital imaging system using the dorsal skin fold chamber, which allows for serial, non-invasive imaging of tumor cells and replication of a fusogenic and a hypofusogenic MV. Hypofusogenic virus-infected cells were detected at the earliest 3 days post-infection (dpi), with peak infection around 6 dpi. In contrast, the fusogenic virus replicated faster: infected cells were detectable 1 dpi and cells were killed quickly. Infection foci were significantly larger with the fusogenic virus. Both viruses formed syncytia. The spatial relationships between cells have a major influence on the outcome of therapy with oncolytic viruses.